Down syndrome (DS), due to triplication of human chromosome 21 (HSA21) (Lejeune et al., 1959), results in a number of significant neurobiological and somatic phenotypes. The most salient are cognitive and behavioral impairments in children and the emergence of Alzheimer’s disease in the elderly (Belichenko et al., 2016; Dierssen, 2012; Dykens, 2007; Kleschevnikov et al., 2012c; Lott, 2012; Nadel, 2003; Roizen and Patterson, 2003; Roper and Reeves, 2006; Sabbagh and Edgin, 2016). The gene-dosage hypothesis proposes that all DS-related phenotypes are due to the presence in excess of one or more genes or regulatory sequences on HSA21 (Epstein et al., 1981). Tests of this hypothesis has in recent years resulted in insights into a number of the genes and mechanisms responsible for DS phenotypes (Belichenko et al., 2009; Dierssen et al., 2011; Fotaki et al., 2002; Kleschevnikov et al., 2004; Olson et al., 2004b; Salehi et al., 2006; Vesa et al., 2005).
